Left Ventricular Diastolic Function and Exercise Capacity in Patients with Chagas Cardiomyopathy

Parameters of diastolic function have been shown to correlate with exercise capacity (EC) in individuals with impaired left ventricular (LV) systolic function. However, the role of LV diastolic function in predicting EC in Chagas cardiomyopathy has not been reported. Objectives: This study aimed to determine the relationship between LV diastolic parameters assessed by echocardiography and EC in patients with Chagas cardiomyopathy. Methods: We studied 40 patients (23 men; 49 ± 8 years), with diagnosis of Chagas disease and dilated cardiomyopathy. Medical therapy was individually adjusted according to standardized guidelines. Methods of acquiring two‐dimensional Doppler, tissue Doppler imaging (TDI), and their measurements were described. Exercise testing was performed by a Bruce protocol. Brain natriuretic peptide (BNP) levels were also determined. Results: Most patients (63%) were in NYHA functional class I. Mean peak oxygen consumption estimated (peakVO₂) was 31.7 ± 10.2 mL/kg per minute, and mean left ventricular ejection fraction (LVEF) was 36.3 ± 7.8%. Univariate analysis showed that various echocardiographic parameters of diastolic function were correlated with peakVO₂. There was no correlation between BNP levels or LVEF and EC. Multivariate analysis, after adjustment for age and gender, revealed that E/E′ ratio and left atrial volume (LAV), emerged as independent predictors of EC, as demonstrated in the model: peakVO₂= 60.825 + (0.439 × LAV) ? (1.620 × E/E′ ratio) ? (0.483 × age) ? (4.821 × female gender). The R² of this model was 0.52. Conclusions: Functional capacity assessed by peakVO₂ was related to increase LV filling pressures, independently on systolic function in patients with Chagas cardiomyopathy. (Echocardiography 2010;27:519‐524)     

Oleic acid modulation of the immune response in wound healing: A new approach for skin repair

Injury triggers inflammatory responses and tissue repair. Several treatments are currently in use to accelerate healing; however, more efficient formulations are still needed for specific injuries. Since unsaturated fatty acids modulate immune responses, we aimed to evaluate their therapeutic effects on wound healing. Skin wounds were induced in BALB/c mice and treated for 5 days with n-3, n-9 fatty acids or vehicle (control). n-9 treated mice presented smaller wounds than control and n-3 at 120 h post-surgery (p.s.). Collagen III mRNA, TIMP1 and MMP9 were significantly elevated in n-9 group compared to n-3 or vehicle at 120 h p.s. Among the inflammatory mediators studied we found that IL-10, TNF-α and IL-17 were also higher in n-9 treated group compared to n-3 or vehicle at 120 h p.s. Interestingly, COX2 had decreased expression on wound tissue treated with n-9. Inflammatory infiltrate analysis revealed diminished frequency of CD4⁺, CD8⁺ and CD11b⁺ cells in n-9 wounds at 24 and 120 h p.s., which was not related to cell death, since in vitro apoptosis experiments did not show any cell damage after fatty acids administration. These results suggested that unsaturated fatty acids, specifically n-9, modulate the inflammation in the wound and enhance reparative response in vivo. n-9 may be a useful tool in the treatment of cutaneous wounds.     

Peroxiredoxin I is overexpressed in oncocytic lesions of salivary glands

Background:  Oncocytic lesions, particularly frequent in the salivary glands, are characterized by cells with an atypical accumulation of mitochondria. This accumulation has been recognized as a compensatory mechanism to intrinsic functional defects of these organelles, resulting in energy production impairment and increased generation of reactive oxygen species (ROS), including hydrogen peroxide (H₂O₂). Peroxiredoxin I (Prx I) is a H₂O₂ scavenging protein and the expression of its yeast homolog was reported to be influenced by mitochondrial function.
Methods:  In this study, we evaluated Prx I expression in oncocytic lesions of salivary glands by immunohistochemistry.
Results:  Our results showed that Prx I is overexpressed in oncocytes regardless of the salivary gland lesion where they appear.
Conclusions:  These results suggest that Prx I expression in oncocytes is related to its ability to decompose mitochondrial-derived H₂O₂ and that it could provide to the cells a protective role in an environment that, by continuously producing potential DNA-damaging ROS, predisposes to genome instability and cellular transformation.     

Quality of life after surgery for temporal lobe epilepsy: A 5-year follow-up

The authors carried out a 5-year prospective study about the effects epilepsy surgery can have on a patient’s quality of life (QOL). They looked for the relationship between improvement on QOL after surgery and reduction of seizure frequency, seizure focus, age at surgery and previous psychopathology. They concluded that improvement in overall, cognitive and social function scores were statistically significant throughout the study. Seizure worry score ceased to be significant at the fifth year. Previous psychopathology was a negative influence on social and seizure worry score. Compared to left lobectomies, right lobectomies showed significant better results in overall scores at six months and one year follow-up. At 1 month follow-up, cognitive function was also significantly better in right lobectomies. Engels class I patients demonstrated statistically better results in the fourth and fifth years of follow-up. Neither years of disease nor patient age at surgery seemed to influence QOL.     

Recessive dystrophic epidermolysis bullosa—oral rehabilitation using stereolithography and immediate endosseous implants

Dental management of patients with epi-dermolysis bullosa (EB) is challenging because of the severe soft tissue lesions associated with this disease. A case history is presented where two immediate endosseous implants were placed in the mandible of a patient with recessive dystrophic EB using computer-aided technology to plan the surgery and prosthetic rehabilitation. After a 24-month follow-up, the prosthesis was stable with healthy asymptomatic soft tissue around the implants. The stereolithographic model provides a precise and noninvasive copy of the mandibular and maxillary arches of patients with EB for rehabilitation of the dentition with immediate endosseous implants and a prosthesis.     

Effects of essential oils from Cymbopogon citratus (DC) Stapf., Lippia sidoides Cham., and Ocimum gratissimum L. on growth and ultrastructure of Leishmania chagasi promastigotes

The current therapy for leishmaniasis, which affects annually about 2 million people, is far from satisfactory. All available drugs require parenteral administration and are potentially toxic. Plant essential oils have been traditionally used in folk medicine and appear as valuable alternative source for chemotherapeutic compounds. In this study, we demonstrated the effect of essential oils from Cymbopogon citratus, Lippia sidoides, and Ocimum gratissimum on growth and ultrastructure of Leishmania chagasi promastigote forms. Steam distillation was used to isolate the essential oils, and their constituents were characterized by gas chromatography coupled to mass spectrometry and nuclear magnetic resonance. All essential oils showed in vitro inhibitory action on L. chagasi promastigotes growth in a dose-dependent way, with IC₅₀/72 h of 45, 89, and 75 μg/mL for C. citratus, L. sidoides, and O. gratissimum, respectively. Drastic morphological alterations were observed in all essential oil-treated parasites, including cell swelling, accumulation of lipid droplets in the cytoplasm, and increase of acidocalcisome volume. Furthermore, aberrant-shaped cells with multi-septate body were observed by scanning electron microscopy, suggesting an additional effect on cytokinesis. Taken together, our data show that these essential oils affect the parasite viability being the C. citratus essential oil the most effective against L. chagasi.     

Susceptibility of Trypanosoma evansi to cordycepin

Drugs, which are effective during the early stage of trypanosomosis, but poorly penetrate the blood-brain barrier, are ineffective when parasites reach the brain and cause encephalitis. In order to seek alternative treatments, the aim of this study was to test the susceptibility of T. evansi to cordycepin in vitro and in rats experimentally infected. In vitro, a significant decrease (P < 0.01) in live trypanosomes in the concentrations of 5.0 and 10 μg/mL was observed 1 hour after the beginning of the study, as well as at 3, 6, 9 and 12 hours in all concentrations compared to control. Although no curative effects were observed in the in vivo assay in the majority of groups, the drug was able to maintain parasitemia at low levels, therefore increasing the longevity of rats when compared to positive control group. Rats that received cordycepin alone or in combination with adenosine deaminase inhibitor (ADA: EHNA hydrochloride), did not show trypomastigote forms of the parasite in the bloodstream 24 hours after the administration. These animals remained negative in blood smears on average for 8 days, but thereafter had a recurrence of parasitemia. Among all the infected animals, only three rats in the group treated with the combination of cordycepin (2 mg/kg) and EHNA hydrochloride (2 mg/kg) remained negative during the experimental period. The curative efficacy of 42.5% was confirmed by PCR using T. evansi-specific primers. Thus, we conclude that cordycepin has biological effect against T. evansi, as previously reported in infections by T. brucei, T. cruzi and Leishmania sp. The treatment with cordycepin, when protected by an inhibitor of ADA, can prolong the survival of T. evansi-infected rats and provide curative efficacy.     

Therapy of adrenocortical cancer: present and future

Adrenocortical carcinoma is a rare endocrine malignancy with an estimated worldwide incidence of 0.5 - 2 per million/year. This neoplasm is characterized by a high risk of recurrence and a dismal prognosis owing to unsatisfactory overall survival. Surgery represents the cornerstone of adrenocortical carcinoma therapy, which can be associated to radiotherapy and adjuvant mitotane administration. In advanced cases, different chemotherapy regimens are used, but their relative efficacy is still unknown until the results of clinical trials under way will be published. Novel drugs have been recently developed based on the discovery of molecular pathways that trigger development and evolution of these tumors. More efficient treatments are widely expected in the future from these new targeted therapies as a hope of cure for patients affected with this aggressive malignancy.